POLR2F

Chr 22

RNA polymerase II, I and III subunit F

Also known as: HRBP14.4, POLRF, RPABC14.4, RPABC2, RPB14.4, RPB6, RPC15

NCBI Gene: 5435ENSG00000100142UniProt: P61218OMIM: 604414

The protein encoded by this gene is the sixth largest subunit of RNA polymerase II and serves as a common component of RNA polymerases I, II, and III, which are responsible for transcribing DNA into various types of RNA including mRNA, ribosomal RNA, and transfer RNA. Mutations in POLR2F cause autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and brain atrophy. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.88
Clinical Summary— POLR2F
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
214 unique Pathogenic / Likely Pathogenic· 158 VUS of 531 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.013
Z-score 1.87
OE 0.42 (0.22–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.89Z-score
OE missense 0.73 (0.59–0.90)
61 obs / 83.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.22–0.88)
0≤0.351.4
Missense OE0.73 (0.59–0.90)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 5 / 12.0Missense obs/exp: 61 / 83.8Syn Z: 0.46
DN
0.74top 25%
GOF
0.5169th %ile
LOF
0.2484th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

531 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic127
Likely Pathogenic87
VUS158
Likely Benign94
Benign20
Conflicting26
127
Pathogenic
87
Likely Pathogenic
158
VUS
94
Likely Benign
20
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
92
13
22
0
127
Likely Pathogenic
54
28
5
0
87
VUS
7
137
10
4
158
Likely Benign
0
8
16
70
94
Benign
0
4
14
2
20
Conflicting
—26
Total1531906776512

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

POLR2F · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Chronic kidney disease onset, progression, and cardiovascular outcomes: proteomics informs biology and risk stratification.
Zhang J et al.·Cardiovasc Diabetol
2026
Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.
Armstrong NJ et al.·Stroke
2020Meta-analysis
Purine metabolism-related genes and immunization in thyroid eye disease were validated using bioinformatics and machine learning.
Wu Z et al.·Sci Rep
2023
Two miRNA prognostic signatures of head and neck squamous cell carcinoma: A bioinformatic analysis based on the TCGA dataset.
Wu C et al.·Cancer Med
2020
Predicting the influence of homologous recombination repair deficiency genes on glioma heterogeneity and patient prognosis using multi-omics analysis and machine learning.
Wu X et al.·PLoS One
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients